CA1059024A - 1,2-dialkyl-3(or 3,5)-n-heterocyclic pyrazolium salts or derivatives thereof as fungicidal agents - Google Patents
1,2-dialkyl-3(or 3,5)-n-heterocyclic pyrazolium salts or derivatives thereof as fungicidal agentsInfo
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- CA1059024A CA1059024A CA247,510A CA247510A CA1059024A CA 1059024 A CA1059024 A CA 1059024A CA 247510 A CA247510 A CA 247510A CA 1059024 A CA1059024 A CA 1059024A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/16—Halogen atoms or nitro radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
Abstract of the Disclosure There is provided a method for controlling fungi with a fungicidally effective amount of a 1,2-dialkyl-3(or 3,5,-N-heterocyclic pyrazolium salt. There is also provided a method for protecting living plants from attack by fungi through the application to the foliage of said plants or a fungicidally effective amount of such pyrazolium salt compounds.
Description
The present invention relates to a method for con-trolling fungi with pyrazolium compounds which have a nitro-gen containing heterocyclic group either in the 3 position, or in the 5 position or in the 3 and 5 positions of the pyra-zolium ring and are represented by a formula:
~H3 ~
(I) R5 ~ IN_CH3 O X-m - ¦ C~3 wherein R3 is a member selected from the group consisting of hydrogen, methyl, hydroxy and phenyl, R4 represents a member selected from the group consisting of hydrogen or halogen;
R5 represents a member selected from the group consisting of phenyl, cyclohexyl and - ~ H2)n; X represents an anion wlth a charge of 1 or 2 and preferably 1; n represents an integer selected from 4, 5 and 6; m represents an integer selected from 1 and 2; and HB represents an inorganic or organic acid.
As employed in the present application the term "halogen" is intended to mean fluorine, chlorine, bromine and iodine; however, bromine is preferred.
Illustrative of the anions, represented by X, which are suitable for use in the present invention are, for exam-ple, halides such as chloride, bromide or iodide; acetate;
sulfate, hydroxide; hydrogen sulfate; methyl sulfate; benzene sulfonate; alkoxy (Cl-C4) benzene sulfonate; alkyl (Cl-C3) benzene sulfonate, such as, p-toluene sulfonate; nitrate;
phosphate; tetrafluoroborater (C6Hs)4B; iodate; alkane sulfo-nate (Cl-C4); perchlorate; 8r3 and I3 .
With regard to the pyrazolium salts of formula (I), -1- $~
1059~1Z4 it is to be understood that certain multivalent anions such as sulfate, phosphate, and the like may have associated with them a cation in addition to the pyrazolium, as for example a proton or an alkali metal or alkaline earth metal. For simplicity, such anions are characterized as being unionized, although they probably are further ionized in fact. Typical representations are: NaS04 , KP0~ , MgP04 , HS04 , and NaHPO4 Illustrative of the acid residue, identified in ~ormula(II)above as HB, which is suitable for use in the . present invention are (a) inorganic acids, such as HCl, HI, B r, HC10~, H2S04, HN0~ and H3P04 and (b) organic acids, such as CH3SO3H, CH3 ~ SO3H, ClCHzCOOH~ and other organic acids of sufficient acid strength to form stable salts with N ~CH2)n group.
3 Preferred compounds useful for the practice of the method of this invention are represented by above-identified formulas (I) and (II), respectively, wherein R3 is hydrogen or methyl; R4 is hydrogen, R5 is phenyl, or cyclohexyl; n is 5; m is 1 or 2; and X is an anion with a charge of 1 or 2.
Exemplary of the effective compounds useful in the present invention are:
1,2-Dimethyl-3-phenyl-5-piperidinopyrazolium iodide, hydro-iodide, 1,2-Dimethyl-3-phenyl-5-piperidinopyrazolium perchlorate, perchloric acid salt, 1,2-Dimethyl-3-phenyl-5-(1-pyrrolidinyl)pyrazolium methyl sulfat.e, 3-(Hexahydro-lH-azepin-1-yl)-1,2-dimethyl-5-phenylpyrazolium iodide, 1,2-Dimethyl-3-(4-methylpiperidino)-5-phenylpyrazolium iodide, 1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyraz~lium iodide, _ ~ _ ` ` lOS9OZ4 1,2-Dimethyl-3-(3-methylpiperldino)-5-phenylpyrazolium iodide, 4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium bromide, hydrobromide, 4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium perchlorate, perchloric acid salt, 1,2-Dimethyl-3,5-dipiperidinopyrazolium bromide, nitric acid saltj 1,2-Dimethyl-3,5-dipiperidinopyrazolium perchlorate, 1,2-Dimethyl-3-~3-methylpiperidino)-5-phenylpyrazolium perchlorate, 1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium bromide, 1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium methyl sulfate, 1,2-Dimethyl-3-(3-piperidino)-5-phenylpyrazolium chloride, 1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium methyl sulfate, 3-Cyclohexyl-1,2-dimethyl-5-(3-methylpiperidino)pyrazolium methyl sulfate (and chloride), 1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium per-chlorate, 1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium chloride hydrochloride, 3-Cyclohexyl-1,2-dimethyl-5-(3-methylpiperidino)pyrazolium iodide, ~5 3-Cyclohexyl-1,2-dimethyl-5-piperidinopyrazolium iodide, 1,2-Dimethyl-3-(3-hydroxypiperidino)-5-phenylpyrazolium iodide, In accordance with the invention,compounds of formula (I) defined above can be synthesized from an inter-mediate (IV), defined below, by reaction of the intermediate 3-halopyrazolium compounds (IV) with a saturated azahetero-cycle or a saturated N-containing heterocycle (III) herein-below defined within a temperature range of from about 20C.
3 _ to about 100C. In this reactlon it is necessary to include either two moles of the azaheterocycle, one as a base acceptor, or to use one mole of azaheterocycle and one mole of an organic or inorganlc base acceptor. In practice tertiary amines, such as trimethylamine, triethylamine, pyridine or quinoline as well as inorganic bases, such as sodium bicarbonate, sodium carbonate and the like can be employed.
The reaction is graphically illustrated as "Method 10 A" aS follows:
R - ~ H -m ~ ~ ~ n~
R4 R4 R3 ~
_ ~ _ m (IV) (III) (I) where R3, R4, R5, m, n and X are each as defined above. This reaCtion involves displacement of a halogen by a azahetero-. cycle group. Additionally a variety of inert solvents such as methanol, ethanol, propanol, dimethylformamide (DMF) 9 acetone, acetonitrile or the llke can be utilized during reaction, A limitation to this procedure is reaction tempe-rature and time. Heating the (IV) compound with an excess of azaheterocycle, especially at temperatures above 100C.
over an extended time, causes increasing dealkylation of the pyrazolium compound (I) to the oyrazole. Thus, to prevent dealkylation, the preferred reaction temperature is 80C., or less, and preferably 40C. to 80C.
The counter ion X employed in the Method A may be any of those listed, although methyl sulfate, iodide, bromide, chloride, perchlorate, and tetrafluoroborate are generally .
1059(1124 preferred. The product identified by formula (I) may be prepared with a particular anion X either by reacting compound IV containing the required anion X or by alternative proce-dures outlined below. For example, the anion of(~ may be replaced either by exchange chromatography (Method A) on an appropriately modified Dowex l-X8 base anion exchanged or in some cases by the addition of a concentrated solution of an acid salt (Method A salt) e.g. utilizing sodium iodide, sodim tetrafluoroborate, or sodium perchlorate [or 10~ aqueous perchloric acid (Method A acid)j, thereby causing the water insoluble salt to precipitate. Whe~ an acid is used as, for instance, perchloric acid, not only does ion exchange occur, but there also may occur the formation of a perchlorate salt of the azaheterocyclic group.
Purification of a formula (I) compound above can be effected by dissolving said compound in water, excepting the water insoluble salts, such as perchlorate or iodide, and washing the aqueous layer with ether, discarding the ether layer, then extracting the same with chloroform or methylene chloride. Product (I) may then be precipitated from the chlorinated hydrocarbon by the addition of diethyl ether.
The preparation of 3-halopyrazolium compound ~V) employed in Method A can be accomplished by the stepwise reactions involving: (1) a benzoyl acetic acid ester or a cycloalkanoyl acetic acid ester (V) defined more particularly hereinbelow with methyl hydrazine to yield a 3-pyrazolinones (VI), (2) halogenation of said pyrazolinone (VI) with phos-phorus oxyhalide to yield the corresponding 3-halopyrazole (VII) and, (3) methylation of said 3-halopyrazole (VII) to yield a 3-hal~pyrazolium com~ound (IV). Converslon of the formula (IV) 3-halopyrazolum salt to the formula (~) pyra-zolium salt containing, the 3-nitrogen heterocyclic group is readily achieved by reactlon of the halopyrazolium salt with lOS90Z4 an azaheterocycle in the presence of base, as described aboveO
The four reaction steps are graohically lllustrated below with phosphorus oxychloride used to represent the oxyhalide employed as the halogenation reagent of the pyrazolinone (VI).
R5-COCHCO2C2H5 + CH3NH-NH2 ) R5_,~,N`N-CH3 (1 ) R4 R~
(V) (VI ) R5--~ o POCl ~ R~.Cl (VI) . (VII) R5~"N~ N-CH3 Rs ~ ~N-CH3 . x-m (3 ) R~ Cl ~ethvlation~ L R~ Cl (VII) (IV) m ~ .
(4 j CH3 1 I C~
. ~5~ -CH3 ¦ X m + H~H2)base> Rs~ ~-CH3 I-X
Cl I R3 ~ R3 ~m (IV) (I) .
where R3, R4, R5, m and n are each as defined above.
The methylation reaction in Step 3 above is preferably conducted in the presence of a solvent, such as xylene, toluene, benzene, l,2-dichloroethane or the like.
Alternativelyj it may be conducted to the exclusion of a solvent using solely the halopyrazole (VII) reactant and the alkylating agent.
Illustrative methylation reagents include, methyl sulfate, methyl halides, methyl hydrogen sulrateJ methyl toluene sulfonate and the like.
~059024 In ~eneral,the halopyrazole and methylatlng reagent eombine on an equimolar basis. However, it is a good practice to employ an excess of the methylating agent. Optimum reae-tion eonditions for effeeting the methylations will vary depending on the reaetants employed. Reaction is effeeted by eombining the methylating agent and an halopyrazole usually in the presence of a solvent. The reaction mixture is heated until the reaction oecurs. Where the methylating reagents employed are volatile, such as methyl chloride, the reaction is preferably conducted in a sealed vessel under pressure, to avoid loss of the reactants. The qUaternizatIOn of the formula (IV) 3-halopyrazolium compound is accomplished by utilizing a methylating agent, such as dimethylsulfate, methyl ehloride, methyl iodide or other sueh agent, alone or admixed with a solvent. ' The preparation of formula (IV) 3-halopyrazolium eompounds where R4 is halogen, ean be accomplished by direct halogenation of the l-methyl-3-halopyrazole (VII) in acetie aeid.
Compounds containing 3,5-disubstituted azahetero-eyelie substituents (IX) ean be prepared by a proeess, here-inafter referred to as Method B. This method involves the reaetion of a 3,5-dihalopyrazolium compound with an azahetero-'cycle; both 3 and 5-dihalogens react rapidly at ambient temperatures up to 80C. However, under these eonditions, the substituent in the 4-position, even a 4-halogen, is un-reaetive to an azaheterocycle. The reaction is preferably eonducted in the presenee of a base and an aprotic solvent such as xylene, toluene, benzene or the like. This reaction "Method B" is graphically illustrated as follows:
1059C~24 CIH3 ~
Hal ~ H3 X m +2H ~ H2)n base _ R4 al R3 accëptor~
(VIII) IH3 where R3, R4, m and n are each as defined above.
In practice it has been found that formula (X) 3,5-diazaheterocyclylaminopyrazolium compounds where R4 is hydrogen, can be most advantageously prepared from formula (IX) ~,5-diazeheterocyclylamino-4-halopyrazolium compounds by a dehydrohalogenation process, hereinafter referred to as "Method C." The process involves the reaction of a 3,5-diazaheterocyclylamino-4-halopyrazolium salt (XI) with hydrogen, in the presence of a strong base sUch as an alkali metal alkoxide (e.g. sodium methoxide, sodium ethoxide or potassium t-butoxide) and a catalyst such as palladium or platinum on carbon. The reaction iS preferably conducted at a temperature between about 20C. and 40C. and may be illUs-trated as follows:
... . . .
Method C
1 3 ~
t ~ ~ -CH3 X m alkali alkoxide _ Hal R ~ H~,+ Pd/C
(XI) ~ ~3 lOS9~24 As noted above, the hereinabove recited compounds are effectlve for the control of fungi which infect many living plants. They are particularly efrective for control-ling powdery mildew, especially on grains such as barley, corn, sorghum and wheat, on vines such as cucumbers, grapes and pumpkin and on fruit and nut trees such as apples, pears and pecans. However, they are also effective for control-ling fungi which are the causative agents for other diseases such as rice blast, and apple scab.
10In utilizing the above-Ldentified pyrazolium salts for protecting plants from pathogenic fungi, it has been found most advantageous to apply the compounds herein foliage of the plant in the form of a liquid, preferably aqueous, spray. Solutions or suspensions containing from 15about 100 to 5500 ppm, and preferably 100 to 1000 ppm of the pyrazolium salt, are generally highly effective for this use.
For application as liquid sprays, said compounds are generally prepared as emulsifiable concentrates, wettable powders, or water miscible concentrates which are diluted with water or other suitable polar solvents, and then applied as a dilute spray. Generally such sprays are applied at the volume rate of about 938 liters to 1877 liters/hectare (l/ha) or about 100 or 200 gal per acre. It is, of course, obvious that smaller or larger volumes of liquid spray may be empl~Æd, eg., 400 to 4000 l/ha may be used depending on a variety of factors including the type of crop, the plant spacing and the amount of foliage per plant being treated.
Wettable oowder formulations can be prepared by ~0 grinding together about ~5~ to 95~ by weight of the pyrazolium -salt and about 75;~ to 5~ by weight of a solid diluent such as attapulgite, kaolin, bentonite, diatomaceous earth, silica, talc, fullers earth or the like. To this mixture is added _ g _ lOS9OZ4 about 1~ to 5~ by weight of a dispersing agent,such as the calcium salt of a polymerized alkyl aryl sulfonic acid, sodium lignosulfonate, or sodium salt of condensed naph-th~lene sulfonic acld,and about 1,~ to 5~ by weight of a surfactant, such as polyoxyethylated vegetable oil, alkyl phenoxy polyoxyethylene ethanol, sodium alkyl naphthalene sul~onate,is also blended with the formulation.
The ~ater-miscible concentrates are prepared by dissolving from 15~ to 70~ by weight of the compound in 85%
to 30~ by weight of a water-miscible solvent, such as water itself or another polar water-miscible solvent, such as
~H3 ~
(I) R5 ~ IN_CH3 O X-m - ¦ C~3 wherein R3 is a member selected from the group consisting of hydrogen, methyl, hydroxy and phenyl, R4 represents a member selected from the group consisting of hydrogen or halogen;
R5 represents a member selected from the group consisting of phenyl, cyclohexyl and - ~ H2)n; X represents an anion wlth a charge of 1 or 2 and preferably 1; n represents an integer selected from 4, 5 and 6; m represents an integer selected from 1 and 2; and HB represents an inorganic or organic acid.
As employed in the present application the term "halogen" is intended to mean fluorine, chlorine, bromine and iodine; however, bromine is preferred.
Illustrative of the anions, represented by X, which are suitable for use in the present invention are, for exam-ple, halides such as chloride, bromide or iodide; acetate;
sulfate, hydroxide; hydrogen sulfate; methyl sulfate; benzene sulfonate; alkoxy (Cl-C4) benzene sulfonate; alkyl (Cl-C3) benzene sulfonate, such as, p-toluene sulfonate; nitrate;
phosphate; tetrafluoroborater (C6Hs)4B; iodate; alkane sulfo-nate (Cl-C4); perchlorate; 8r3 and I3 .
With regard to the pyrazolium salts of formula (I), -1- $~
1059~1Z4 it is to be understood that certain multivalent anions such as sulfate, phosphate, and the like may have associated with them a cation in addition to the pyrazolium, as for example a proton or an alkali metal or alkaline earth metal. For simplicity, such anions are characterized as being unionized, although they probably are further ionized in fact. Typical representations are: NaS04 , KP0~ , MgP04 , HS04 , and NaHPO4 Illustrative of the acid residue, identified in ~ormula(II)above as HB, which is suitable for use in the . present invention are (a) inorganic acids, such as HCl, HI, B r, HC10~, H2S04, HN0~ and H3P04 and (b) organic acids, such as CH3SO3H, CH3 ~ SO3H, ClCHzCOOH~ and other organic acids of sufficient acid strength to form stable salts with N ~CH2)n group.
3 Preferred compounds useful for the practice of the method of this invention are represented by above-identified formulas (I) and (II), respectively, wherein R3 is hydrogen or methyl; R4 is hydrogen, R5 is phenyl, or cyclohexyl; n is 5; m is 1 or 2; and X is an anion with a charge of 1 or 2.
Exemplary of the effective compounds useful in the present invention are:
1,2-Dimethyl-3-phenyl-5-piperidinopyrazolium iodide, hydro-iodide, 1,2-Dimethyl-3-phenyl-5-piperidinopyrazolium perchlorate, perchloric acid salt, 1,2-Dimethyl-3-phenyl-5-(1-pyrrolidinyl)pyrazolium methyl sulfat.e, 3-(Hexahydro-lH-azepin-1-yl)-1,2-dimethyl-5-phenylpyrazolium iodide, 1,2-Dimethyl-3-(4-methylpiperidino)-5-phenylpyrazolium iodide, 1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyraz~lium iodide, _ ~ _ ` ` lOS9OZ4 1,2-Dimethyl-3-(3-methylpiperldino)-5-phenylpyrazolium iodide, 4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium bromide, hydrobromide, 4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium perchlorate, perchloric acid salt, 1,2-Dimethyl-3,5-dipiperidinopyrazolium bromide, nitric acid saltj 1,2-Dimethyl-3,5-dipiperidinopyrazolium perchlorate, 1,2-Dimethyl-3-~3-methylpiperidino)-5-phenylpyrazolium perchlorate, 1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium bromide, 1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium methyl sulfate, 1,2-Dimethyl-3-(3-piperidino)-5-phenylpyrazolium chloride, 1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium methyl sulfate, 3-Cyclohexyl-1,2-dimethyl-5-(3-methylpiperidino)pyrazolium methyl sulfate (and chloride), 1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium per-chlorate, 1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium chloride hydrochloride, 3-Cyclohexyl-1,2-dimethyl-5-(3-methylpiperidino)pyrazolium iodide, ~5 3-Cyclohexyl-1,2-dimethyl-5-piperidinopyrazolium iodide, 1,2-Dimethyl-3-(3-hydroxypiperidino)-5-phenylpyrazolium iodide, In accordance with the invention,compounds of formula (I) defined above can be synthesized from an inter-mediate (IV), defined below, by reaction of the intermediate 3-halopyrazolium compounds (IV) with a saturated azahetero-cycle or a saturated N-containing heterocycle (III) herein-below defined within a temperature range of from about 20C.
3 _ to about 100C. In this reactlon it is necessary to include either two moles of the azaheterocycle, one as a base acceptor, or to use one mole of azaheterocycle and one mole of an organic or inorganlc base acceptor. In practice tertiary amines, such as trimethylamine, triethylamine, pyridine or quinoline as well as inorganic bases, such as sodium bicarbonate, sodium carbonate and the like can be employed.
The reaction is graphically illustrated as "Method 10 A" aS follows:
R - ~ H -m ~ ~ ~ n~
R4 R4 R3 ~
_ ~ _ m (IV) (III) (I) where R3, R4, R5, m, n and X are each as defined above. This reaCtion involves displacement of a halogen by a azahetero-. cycle group. Additionally a variety of inert solvents such as methanol, ethanol, propanol, dimethylformamide (DMF) 9 acetone, acetonitrile or the llke can be utilized during reaction, A limitation to this procedure is reaction tempe-rature and time. Heating the (IV) compound with an excess of azaheterocycle, especially at temperatures above 100C.
over an extended time, causes increasing dealkylation of the pyrazolium compound (I) to the oyrazole. Thus, to prevent dealkylation, the preferred reaction temperature is 80C., or less, and preferably 40C. to 80C.
The counter ion X employed in the Method A may be any of those listed, although methyl sulfate, iodide, bromide, chloride, perchlorate, and tetrafluoroborate are generally .
1059(1124 preferred. The product identified by formula (I) may be prepared with a particular anion X either by reacting compound IV containing the required anion X or by alternative proce-dures outlined below. For example, the anion of(~ may be replaced either by exchange chromatography (Method A) on an appropriately modified Dowex l-X8 base anion exchanged or in some cases by the addition of a concentrated solution of an acid salt (Method A salt) e.g. utilizing sodium iodide, sodim tetrafluoroborate, or sodium perchlorate [or 10~ aqueous perchloric acid (Method A acid)j, thereby causing the water insoluble salt to precipitate. Whe~ an acid is used as, for instance, perchloric acid, not only does ion exchange occur, but there also may occur the formation of a perchlorate salt of the azaheterocyclic group.
Purification of a formula (I) compound above can be effected by dissolving said compound in water, excepting the water insoluble salts, such as perchlorate or iodide, and washing the aqueous layer with ether, discarding the ether layer, then extracting the same with chloroform or methylene chloride. Product (I) may then be precipitated from the chlorinated hydrocarbon by the addition of diethyl ether.
The preparation of 3-halopyrazolium compound ~V) employed in Method A can be accomplished by the stepwise reactions involving: (1) a benzoyl acetic acid ester or a cycloalkanoyl acetic acid ester (V) defined more particularly hereinbelow with methyl hydrazine to yield a 3-pyrazolinones (VI), (2) halogenation of said pyrazolinone (VI) with phos-phorus oxyhalide to yield the corresponding 3-halopyrazole (VII) and, (3) methylation of said 3-halopyrazole (VII) to yield a 3-hal~pyrazolium com~ound (IV). Converslon of the formula (IV) 3-halopyrazolum salt to the formula (~) pyra-zolium salt containing, the 3-nitrogen heterocyclic group is readily achieved by reactlon of the halopyrazolium salt with lOS90Z4 an azaheterocycle in the presence of base, as described aboveO
The four reaction steps are graohically lllustrated below with phosphorus oxychloride used to represent the oxyhalide employed as the halogenation reagent of the pyrazolinone (VI).
R5-COCHCO2C2H5 + CH3NH-NH2 ) R5_,~,N`N-CH3 (1 ) R4 R~
(V) (VI ) R5--~ o POCl ~ R~.Cl (VI) . (VII) R5~"N~ N-CH3 Rs ~ ~N-CH3 . x-m (3 ) R~ Cl ~ethvlation~ L R~ Cl (VII) (IV) m ~ .
(4 j CH3 1 I C~
. ~5~ -CH3 ¦ X m + H~H2)base> Rs~ ~-CH3 I-X
Cl I R3 ~ R3 ~m (IV) (I) .
where R3, R4, R5, m and n are each as defined above.
The methylation reaction in Step 3 above is preferably conducted in the presence of a solvent, such as xylene, toluene, benzene, l,2-dichloroethane or the like.
Alternativelyj it may be conducted to the exclusion of a solvent using solely the halopyrazole (VII) reactant and the alkylating agent.
Illustrative methylation reagents include, methyl sulfate, methyl halides, methyl hydrogen sulrateJ methyl toluene sulfonate and the like.
~059024 In ~eneral,the halopyrazole and methylatlng reagent eombine on an equimolar basis. However, it is a good practice to employ an excess of the methylating agent. Optimum reae-tion eonditions for effeeting the methylations will vary depending on the reaetants employed. Reaction is effeeted by eombining the methylating agent and an halopyrazole usually in the presence of a solvent. The reaction mixture is heated until the reaction oecurs. Where the methylating reagents employed are volatile, such as methyl chloride, the reaction is preferably conducted in a sealed vessel under pressure, to avoid loss of the reactants. The qUaternizatIOn of the formula (IV) 3-halopyrazolium compound is accomplished by utilizing a methylating agent, such as dimethylsulfate, methyl ehloride, methyl iodide or other sueh agent, alone or admixed with a solvent. ' The preparation of formula (IV) 3-halopyrazolium eompounds where R4 is halogen, ean be accomplished by direct halogenation of the l-methyl-3-halopyrazole (VII) in acetie aeid.
Compounds containing 3,5-disubstituted azahetero-eyelie substituents (IX) ean be prepared by a proeess, here-inafter referred to as Method B. This method involves the reaetion of a 3,5-dihalopyrazolium compound with an azahetero-'cycle; both 3 and 5-dihalogens react rapidly at ambient temperatures up to 80C. However, under these eonditions, the substituent in the 4-position, even a 4-halogen, is un-reaetive to an azaheterocycle. The reaction is preferably eonducted in the presenee of a base and an aprotic solvent such as xylene, toluene, benzene or the like. This reaction "Method B" is graphically illustrated as follows:
1059C~24 CIH3 ~
Hal ~ H3 X m +2H ~ H2)n base _ R4 al R3 accëptor~
(VIII) IH3 where R3, R4, m and n are each as defined above.
In practice it has been found that formula (X) 3,5-diazaheterocyclylaminopyrazolium compounds where R4 is hydrogen, can be most advantageously prepared from formula (IX) ~,5-diazeheterocyclylamino-4-halopyrazolium compounds by a dehydrohalogenation process, hereinafter referred to as "Method C." The process involves the reaction of a 3,5-diazaheterocyclylamino-4-halopyrazolium salt (XI) with hydrogen, in the presence of a strong base sUch as an alkali metal alkoxide (e.g. sodium methoxide, sodium ethoxide or potassium t-butoxide) and a catalyst such as palladium or platinum on carbon. The reaction iS preferably conducted at a temperature between about 20C. and 40C. and may be illUs-trated as follows:
... . . .
Method C
1 3 ~
t ~ ~ -CH3 X m alkali alkoxide _ Hal R ~ H~,+ Pd/C
(XI) ~ ~3 lOS9~24 As noted above, the hereinabove recited compounds are effectlve for the control of fungi which infect many living plants. They are particularly efrective for control-ling powdery mildew, especially on grains such as barley, corn, sorghum and wheat, on vines such as cucumbers, grapes and pumpkin and on fruit and nut trees such as apples, pears and pecans. However, they are also effective for control-ling fungi which are the causative agents for other diseases such as rice blast, and apple scab.
10In utilizing the above-Ldentified pyrazolium salts for protecting plants from pathogenic fungi, it has been found most advantageous to apply the compounds herein foliage of the plant in the form of a liquid, preferably aqueous, spray. Solutions or suspensions containing from 15about 100 to 5500 ppm, and preferably 100 to 1000 ppm of the pyrazolium salt, are generally highly effective for this use.
For application as liquid sprays, said compounds are generally prepared as emulsifiable concentrates, wettable powders, or water miscible concentrates which are diluted with water or other suitable polar solvents, and then applied as a dilute spray. Generally such sprays are applied at the volume rate of about 938 liters to 1877 liters/hectare (l/ha) or about 100 or 200 gal per acre. It is, of course, obvious that smaller or larger volumes of liquid spray may be empl~Æd, eg., 400 to 4000 l/ha may be used depending on a variety of factors including the type of crop, the plant spacing and the amount of foliage per plant being treated.
Wettable oowder formulations can be prepared by ~0 grinding together about ~5~ to 95~ by weight of the pyrazolium -salt and about 75;~ to 5~ by weight of a solid diluent such as attapulgite, kaolin, bentonite, diatomaceous earth, silica, talc, fullers earth or the like. To this mixture is added _ g _ lOS9OZ4 about 1~ to 5~ by weight of a dispersing agent,such as the calcium salt of a polymerized alkyl aryl sulfonic acid, sodium lignosulfonate, or sodium salt of condensed naph-th~lene sulfonic acld,and about 1,~ to 5~ by weight of a surfactant, such as polyoxyethylated vegetable oil, alkyl phenoxy polyoxyethylene ethanol, sodium alkyl naphthalene sul~onate,is also blended with the formulation.
The ~ater-miscible concentrates are prepared by dissolving from 15~ to 70~ by weight of the compound in 85%
to 30~ by weight of a water-miscible solvent, such as water itself or another polar water-miscible solvent, such as
2-methoxy ethanol, methanol, propylene glycol, diethylene glycol, diethylene glycol monoethyl ether, formamide, and methylformamide. Application of the material is made by add-ing a predetermined quantity of the water-miscible concentratè
to a spray tank and applying as such or in combination with additional suitable diluent, such as a further quantity of water or one of the above polar solvents mentioned above.
The Performance of the product in the above formul-ations, which are applied as liquid sprays, is improved by adding a surfactant or blend of surfactants thereto. Con-ventional nonionic surfactants are preferred and the sur-factants are preferably added to the formulation or the spray tank at the rate of 0.1% to 5% by volume to provide good wet-ting of the spray solution on plant foliage.
Suitable nonionic surfactants include alkyl polyoxy-ethylene ethers, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monooleate, alkylarylpolyglcol ethers, alkyl phenol ethoxylates, trimethyl nonyl polyethylene
to a spray tank and applying as such or in combination with additional suitable diluent, such as a further quantity of water or one of the above polar solvents mentioned above.
The Performance of the product in the above formul-ations, which are applied as liquid sprays, is improved by adding a surfactant or blend of surfactants thereto. Con-ventional nonionic surfactants are preferred and the sur-factants are preferably added to the formulation or the spray tank at the rate of 0.1% to 5% by volume to provide good wet-ting of the spray solution on plant foliage.
Suitable nonionic surfactants include alkyl polyoxy-ethylene ethers, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monooleate, alkylarylpolyglcol ethers, alkyl phenol ethoxylates, trimethyl nonyl polyethylene
3 glycol ethers, alkyl phenol ethylene oxide condensates, octyl phenoxy polyethoxy ethanols, nonylphenyl polyethylene glycol ethers, condensates of polyoxy ethylenes, polyoxy propylenes, aliphatic polyet}lers, allphatic po]ye,ters, alkylarly poloxy-lOS90Z4 ethylene glycols, and the like. Especially preferred nonionic surfactants having a hydrophilic-lipophilic balance (HLB) of from 11 to 16. This conventional surfactant classification test is described, for example, at page 232 et seq. of Emul-sion Theory and Practice by Paul Becker, ~leinholt Publishing Corporation, second edition (1965); also available as No.
162 in the American Chemical Society's Monograph Series.
Generally, the plants which are to be protected against attack from fungal organisms are sprayed to run off with solutions or suspensions of the above-identified com-pounds. In practice it has been found that solutions or suspensions containing from about 100 to 5600 ppm of the com-pounds herein and preferably 100 to 1000 ppm of such com-pounds afforded the desired protection.
In order to facilitate a further understanding of the invention, the following examples are presented pri-marily for purposes of illustrating certain more specific details thereof. The invention is not to be deemed limited thereby except as defined in the claims. Unless otherwise noted, the parts are by weight.
Example 1 To determine the effectiveness of the 1,2-dialkyl-3~or 3,5)-mono(or di)lheterocyclic pyrazolium salts as fungi-cidal agents, a variety of pathogenic fungi, host plants and acid salts are used in the following tests. Pathogens, host plants, the method of testing, the rating system used, and the data obtained are set forth below.
Pathogens:
Piricularia oryzae Cavara, the rice blast pathogen.
3~ Venturia inae~ualis (Cke.) Wint. which causes apple scab.
Erysiphe cichoracearum DC, the cause of powdery mildew on cucurbits.
1059~24 Podosphaera leucotricha (E. ~ E.) Salm., the cause of powdery mildew of apples and pears.
Erysiphe graminis f sp. tritici the cause of powdery mildew on wheat.
Eryslphe graminis f. sp. hordei the cause of powdery mildew on barley.
Host Plants:
Rice (Oryza sativa) Cv. Nato) Cucumber (Cucum~s sativus) (Cv. Marketer) Apple (Malus sylvestrisj (Seedling) Wheat (Triticum aestivum Cv. Bonanza) Barley lHordeum vul~are Cv. Larker) Plants are individually grown in 5. o8 cm peat squ~es and assembled in 7.52 cm. x 25.4 pm. pressed fibre containers the week prior to spraying. With exception of rice, barley, and wheatl a single specimen of each species is used. A
separate container is used for those plants in the mildew evaluation. The complete test system is shown below.
Series 1 Series c . . . __ __ Rice: Rice Blast Apple: Powdery Mildew Apple: Apple Scab Cucumber: Powdery Mildew Wheat: Powdery Mildew Barley: Powdery Mildew Spray solutions are prepared at a final concen-tration of 100 ppm or 500 ppm in 50 ml of 50~ a~ueous acetone.
Acetone is added to solubilize the test compound and soluticns made to final volume with deionized water.
~o containers, one each from Series 1 and 2 (see above), are sprayed simultaneously on a turntable with 50 ml of the test solution. Spray is provided by two fixed sprayi~
nozzles mounte~ to deliver vertical and horizontal solid cone spray patterns. Immediately thereafter, all plants are returned to the greenhouse to permit the deposit to dry.
Plants of Series 1 and 2 are separately inoculated. Plants - l? -1059~124 in Series 1 are inoculated with conidlal suspenslons of the respective pathogens using a paint sprayer operated under-
162 in the American Chemical Society's Monograph Series.
Generally, the plants which are to be protected against attack from fungal organisms are sprayed to run off with solutions or suspensions of the above-identified com-pounds. In practice it has been found that solutions or suspensions containing from about 100 to 5600 ppm of the com-pounds herein and preferably 100 to 1000 ppm of such com-pounds afforded the desired protection.
In order to facilitate a further understanding of the invention, the following examples are presented pri-marily for purposes of illustrating certain more specific details thereof. The invention is not to be deemed limited thereby except as defined in the claims. Unless otherwise noted, the parts are by weight.
Example 1 To determine the effectiveness of the 1,2-dialkyl-3~or 3,5)-mono(or di)lheterocyclic pyrazolium salts as fungi-cidal agents, a variety of pathogenic fungi, host plants and acid salts are used in the following tests. Pathogens, host plants, the method of testing, the rating system used, and the data obtained are set forth below.
Pathogens:
Piricularia oryzae Cavara, the rice blast pathogen.
3~ Venturia inae~ualis (Cke.) Wint. which causes apple scab.
Erysiphe cichoracearum DC, the cause of powdery mildew on cucurbits.
1059~24 Podosphaera leucotricha (E. ~ E.) Salm., the cause of powdery mildew of apples and pears.
Erysiphe graminis f sp. tritici the cause of powdery mildew on wheat.
Eryslphe graminis f. sp. hordei the cause of powdery mildew on barley.
Host Plants:
Rice (Oryza sativa) Cv. Nato) Cucumber (Cucum~s sativus) (Cv. Marketer) Apple (Malus sylvestrisj (Seedling) Wheat (Triticum aestivum Cv. Bonanza) Barley lHordeum vul~are Cv. Larker) Plants are individually grown in 5. o8 cm peat squ~es and assembled in 7.52 cm. x 25.4 pm. pressed fibre containers the week prior to spraying. With exception of rice, barley, and wheatl a single specimen of each species is used. A
separate container is used for those plants in the mildew evaluation. The complete test system is shown below.
Series 1 Series c . . . __ __ Rice: Rice Blast Apple: Powdery Mildew Apple: Apple Scab Cucumber: Powdery Mildew Wheat: Powdery Mildew Barley: Powdery Mildew Spray solutions are prepared at a final concen-tration of 100 ppm or 500 ppm in 50 ml of 50~ a~ueous acetone.
Acetone is added to solubilize the test compound and soluticns made to final volume with deionized water.
~o containers, one each from Series 1 and 2 (see above), are sprayed simultaneously on a turntable with 50 ml of the test solution. Spray is provided by two fixed sprayi~
nozzles mounte~ to deliver vertical and horizontal solid cone spray patterns. Immediately thereafter, all plants are returned to the greenhouse to permit the deposit to dry.
Plants of Series 1 and 2 are separately inoculated. Plants - l? -1059~124 in Series 1 are inoculated with conidlal suspenslons of the respective pathogens using a paint sprayer operated under-
4-5 psig and, immediately, are transferred to a controlled temperature/humidity cabinet (ambient temperature, RH~95~).
Plants in Series 2 are dusted with respective powdery mildew conidia and then removed to the controlled environment plant culture room (10 hours light, - 22 C., RH 45~o) to await disease development. Plants ln Series 1 are held 4 days in the cabinet, then~transferred to the greenhouse to await disease expression.
Performance Rating:
. . _ All plants are rated for disease severity on a scale of 1 to 7 (clean to kill), as described belo;l:
Rating Description 1 Clean - 2 Trace disease 3 Slight disease 4 ~ Moderate disease Heavy disease 6 Severe disease 7 Kill In the tables hereinbelow presented, the numerical ~ rating is used for clarity. Data obtained are reported in Tables I and II below. The ratings reported represent data obtained from one or more individual tests. Where more than one test has been conducted, the ratings are averaged and reported as a single value rating. For each table, there is also provided a rating value for the checks employed and a rating range for acceptable disease control. It is, of course, obvious that the lower the value, the more effective the disease control.
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~lOS91~24 Example 2 The fungicidal activity of the compounds of the present lnvention is demonstrated in the following tests.
Wheat plants are individually grown in 5.08 cm peat squares and assembled in containers the week prior to spraying.
Spray solutions are prepared at a final concentration of 500 ppm in 50%/50% water/acetone mixtures. The plants are placed on a turntable and sprayed with 50 ml of test solution. Immediately thereafter they are placed on green-house benches and permitted to dry. After drying, said treat-ed plants are dusted with powdery mildew spores and the dusted plants are then placed in a constant temperature room (22C
10 hours light and 45% RH) for from 7 days to 9 days to await disease expression. At the end of the holding period, all plants are examined and rated according to the performance rating system provided below.
Performance Rating All plants were rated for disease severity on a scale of 1 - 7 (clean - kill), as described in ~:cample I
abo~e.
Data obtained are reported in Table III below.
1059029~
Table III
Control of Powdery Mildew on Wheat Compound Rate Disease ppm Severity 1,2-Dimethyl-3-(3-methylpiperidino)- 500 1-Clean
Plants in Series 2 are dusted with respective powdery mildew conidia and then removed to the controlled environment plant culture room (10 hours light, - 22 C., RH 45~o) to await disease development. Plants ln Series 1 are held 4 days in the cabinet, then~transferred to the greenhouse to await disease expression.
Performance Rating:
. . _ All plants are rated for disease severity on a scale of 1 to 7 (clean to kill), as described belo;l:
Rating Description 1 Clean - 2 Trace disease 3 Slight disease 4 ~ Moderate disease Heavy disease 6 Severe disease 7 Kill In the tables hereinbelow presented, the numerical ~ rating is used for clarity. Data obtained are reported in Tables I and II below. The ratings reported represent data obtained from one or more individual tests. Where more than one test has been conducted, the ratings are averaged and reported as a single value rating. For each table, there is also provided a rating value for the checks employed and a rating range for acceptable disease control. It is, of course, obvious that the lower the value, the more effective the disease control.
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~lOS91~24 Example 2 The fungicidal activity of the compounds of the present lnvention is demonstrated in the following tests.
Wheat plants are individually grown in 5.08 cm peat squares and assembled in containers the week prior to spraying.
Spray solutions are prepared at a final concentration of 500 ppm in 50%/50% water/acetone mixtures. The plants are placed on a turntable and sprayed with 50 ml of test solution. Immediately thereafter they are placed on green-house benches and permitted to dry. After drying, said treat-ed plants are dusted with powdery mildew spores and the dusted plants are then placed in a constant temperature room (22C
10 hours light and 45% RH) for from 7 days to 9 days to await disease expression. At the end of the holding period, all plants are examined and rated according to the performance rating system provided below.
Performance Rating All plants were rated for disease severity on a scale of 1 - 7 (clean - kill), as described in ~:cample I
abo~e.
Data obtained are reported in Table III below.
1059029~
Table III
Control of Powdery Mildew on Wheat Compound Rate Disease ppm Severity 1,2-Dimethyl-3-(3-methylpiperidino)- 500 1-Clean
5-phenylpyrazolium chloride 1,2-Dimethyl-3-(3-methylpiperidino)- 500 l-Clean 5-phenylpyrazolium perchlorate 1,2-Dimethyl-3-t3-methylpiperidino)- 500 l-Clean 5-phenylpyrazolium iodide 1,2-Dimethyl-3-(4-methylpiperidino)- 500 2-Trace 5-phenylpyrazolium iodide _ .
1,2-Dimethyl-3-(2-methylpiperidino)- 500 2-Trace 5-phenylpyrazolium iodide 3-(Hexahydro-lH-azepin-l-yl)-1,2-500 3-Slight dimethyl-5-phenylpyrazolium iodide 1,2-Dimethyl-3-phenyl-5-piperidino- 500 3-Slight pyrazolium iodide From these data it is apparent that 1,2-dimethyl-3-(2,3 or 4-methylpiperidino)-5-phenylpyrazolium salts are preferred fungicidal agents effective for the control of powdery mildew on wheat.
The following examples illustrate the preparation of the compounds employed as fungicides herein.
~ 1 ..
~059~24 Example 3 Preparation of l-methyl-~-phenyl-2-pyrazolin-5-one Ethyl benzoylacetate (1,538 g, 8 moles) dissolved ln lsopropanol (5 1) is placed ln a 12 1 flask under an at-mosphere of nitrogen. Methylhydrazine (410 g, 8.7 moles, 98~) in isopropanol (800 ml) is added with stirring in a dropwise manner to the ethyl benzoylacetate solution pre-warmed to about 80C. During the addition the external heating is removed. Seeding of the reaction mixture with the product at the point of one-third addition of methyl-hydrazlne causes a copious precipitate of product. This procedure eliminates a large exotherm from occurring at a later stage. After the addition is complete~ the reaction mixture ls held at about 80C. for 2 hours. Cooling the slurry to 20C. and filtering off the solid, a yield of 1,131 g (81~) of product after drying with a melting point equal to 211C. is obtained.
Example 4 Preparation of 5-chloro-1-methyl-3-phenylpyrazole To a solution of phosphorous oxychloride (2,015 g, 19 moles) is added solid 1-methyl-3-phenyl?yrazolin-5-one (2,073 g, 11.9 moles) with stirring and warming. At 100C.
the mixture becomes homogeneous. The reflux temperature rises from 119C. to 143C. over a period of 30 hours. After coolln~ the mixture is poured into ice and water (8 1) with stirring. After 4 hours the slurry is filtered and the fllter cake added to 4 1 of water containing 1.5 1 of 10~ sodium hydroxide solution with stirring. Removal of the solid by filtration followed by a recrystallization from hexane yields 1,523 g of product, having a melting point ranging from 51C.
to 52C.
Example 5 Preparation of 3-chloro-1,2-dimethyl-5-~henylpyrazolium methyl sulfate, utilizing one of two methods METHOD (A) Dimethyl sulfate (30 g, 0.22 mole) is added to a stirred solution of 5-chloro-1-methyl-5-phenylpyrazole (39.5 g, 0.2 mole) in dry xylene (350 ml) and the reaction mixture is warmed to 105C. to 115C. for 18 hours. A brown syrup separates out, the reaction is cooled and the xylene is decanted off. Dry acetone (300 ml) is added and after stirring a white precipitate separates out and is filtered off, mp 100C. to 102C. 33.8 g, (55~). Recrystallization from dry acetone-toluene (1:1) gives white needles mp 102C.
to 104C.
Analysis calculated for C12H15N2ClSO4: C, 45.22;
H, 4.74; N, 8.79; Cl, 11.13. Found: C, 45.31; H, 4.81;
N, 8.93; Cl, 11.24.
METHOD (B) To a solution of dimethyl sulfate (1,596 g, 12.66 moles) at 70C. to 74C. is added 5-chloro-1-methyl-3-phenyl-pyrazole (1,523 g, 7.912 moles). During the exothermic ad-dition the heat source is removed. After the exothermic reaction has ceased, the reaction mixture is maintained at 80C. by external heating for 2 hours and then is poured into toluene. Toluene is decanted off, leaving a residual syrup, which is treated with additional toluene and decanted off as above. The syrup is dissolved in chloroform, filtered, and the filtrate evaporated to an oil, which crystallizes from acetone to yield 1.52 kg, (60.3%) mp 95C. to 96C.
Example 6 Preparation of 3-chloro 1,2-dimethyl-5-phenylpyrazolium iodide To an aqueous solution of 1,2-dimethyl-3-chloro-5-phenylpyrazolium methyl sulfate is added a saturated aqueous _ lOS90Z4 solution of sodium iodide at 5C. A copious precipitate is formed and filtered off. The solid is dissolved in methylene chloride and precipitated with diethyl ether to yield almost white crystals mp 152C. to 154C.
Analysis calculated for CllHl2N2Cll: C, 39.49;
H, 3.52; N, 8.38; Cl, 10.54; I, 37.93. Found: C, 39.45;
H, 3.51; N, 8.44; Cl, 10.47; I, 37.85.
Example 7 Preparation of ~-cyclohexyl-l-methyl-2-pyrazolin-5-one To ethyl 3-oxo-cyclohexanepropionic acid (4.4 g, 0.234 molej in n-propanol (500 ml) is added dropwise with stirring under nitrogen at 80C. methylhydrazine (13.8 g, 0.3 mole). After heating at reflux during 5 hours, the reaction is cooled and evaporated to a residual oil. Crystal-lization from ethylacetate ~ives a white powder mp 170.5C.
to 172C.
Analysis calculated for CloHloN20; C, 56.5~ H, 8.95; N, 15.54. Found: C, 55.59; H, 9.07; N, 15.~9.
Example 8 Preparation of 5-chloro-3-cyclohexyl~l-methylpyrazole Phosphoru~ oxychloride (15.3 g, 0.1 mole) is added to 3-cyclohexyl-1-methyl-2-pyrazolin-5-one and the mixture stirred and heated at 120C. to 135C. for 8 hours. The cooled reaction mixture is then poured into ice-water, made alkaline with 1~ aqueous sodium hydroxide and extracted with methylene chloride. Removal of solvent under reduced pressu~, then in vacuo at 70C. affords an oil, 8 g, (93.8~).
Analysis calculated for CloH15N~Cl; C, 50.45;
H, 7.51; N, 14.10; Cl, 17.85. Found: C, 50.c8; H, 7.55;
N, 14.20; Cl, 17.79.
_ ~4 -- : lOS9OZ4 Example 9 Preparation of 3-chloro-5-cyclohexyl-1,2-dimethylpyrazolium methyl sulfate ~and hydrogen sulfate (1:1)]
A mixture of 5-chloro-3-cyclohexyl-1-methylpyrazole (7 g, .0352 mole) and dimethyl sulfate (8.82 g, 0.07 mole) is heated to 80C. and the heating source then removed. The reaction temperature rises to ~8C. and then, after the exo-therm, the temperature is maintained at ~0C. by external heating for 5 hours. Toluene (100 ml) is added to the cooled reaction and the mixture is set aside overnight at room temperature and then a waxy solid is filtered off. Crystal-llzation from methylene chloride-ether affords a granular product, mp 70C. to 73.5C., 11.2 g (100%). NMR and infrared spectra indicate a mixture of CH3S04 and HS04 anions.
Analysis calculated for Cl2H2lN2ClS04 (as CH3S04):
C,44.35; H, 5.57-; N, 8.53; S, 9.&7; Cl, 10.92. Found C, 41.34;
H, 5.24; N, 8.14; S, 9.12; Cl, 10.31.
A portion of the above compound is readily converted to the perchlorate whose melting point ranges from 215C. to 218C.
Example 10 Preparation of 3,4,5-Tribromo-l-methylpyrazole _ .. . . . . .
To 3,4,5-tribromo?yrazole (4.5 g, 0.15 mole) in 3N
aqueous sodium hydroxide (5 g, 0.15 mole) is added at room temperature with stirring dimethyl sulfate (19 g, 0.15 mole).
After 10 minutes a solid separates out. An additional gram of dimethyl sulfate is added and the mixture is stirred for 3 days, filtered and the precipitate water washed and air dried to yield 33 g (73,0), mp 85C. to &5C. Crystallization from cyclohexane yields desired solid product whose melting point ranges from about 90C. to 91C.
Analysis calculated for C4H3N2Br3: C, 15.07; ~, o ~5;
N, 8.79; Br, 75. '1. Found: C, 15.1~; H, 0.~32; N, &.7; Br 75.35.
Example 11 ~rc b ~ r ~ t ~
A stirred suspension of l-methyl-3,4,5-tribromo-pyrazole (19.3 g, 0.05 mole) ln dimethyl sulfate (80 ml) is stirred and heated at 130C. to 135C. for 5 hours. On cooling and setting aside overnight, a solid is obtained and filtered off, benzene washed and ai~ dried to yield 18.7 g, (70~) whose melting point ranges from 199C. to 203C.
lo Analysis calculated for C~H~N2Br3SO4: C, 15.19;
H, 2.04; N, 5.?9; Br, 53.88; S, 7.20. Found: C, 16.19;
H, 1.99; N, 5.38; Br, 53.98; S, 7.31.
Treatment of the above methyl sulfate compound with aqueous perchloric acid affords the perchlorate whose melting point ranges from 300C. to 300.5C.
Example 12 Preparation of 1,2-dimethyl-3-phenyl-5-piperidinopyrazolium iodid~and perchlorate Piperidine (2.56 g, 0.03 mole) is added to 1,2-dimeth~
3-chloro-5-phenylpyrazolium methyl sulfate (4.77 g, 0.015 mole) in absolute ethanol (30 ml) and the mixture stirred with a bar magnet and heated under reflux for 4 hours. After cooling, the reaction mixture is evaporated under reduced pressure to a brown oil, and then dissolved in 50 ml of aqueous saturated sodium bicarbonate solution. The aqueous layer is extracted with ether and this organic layer discarded, then with chloro-form (3x100 ml). Evaporation of the chloroform layer affords 1,2-dimethyl-3-phenyl-5-piperidinopyrazolium methyl sulfate as a viscous oil. The oil is redissolved in water and saturated 3 aqueous potassium iodide solution is added. (Sodium iodide is also equally effective). An immediate copious white precipitat~
of 1,2-dimethyl-3-phenyl-5-piperidinopyrazolium iodide is formed, then filtered and washed with ice cold water to ~ive _ ~f _ ~ 1059024 3.37 g, (56%) Or product mp 179C to 180C. The melting point is unchanged by dissolving in chloroform, filterln~ and repre-cipitating with diethyl ether and filtering Orr the solid.
For analysis see Table ~, compound 1.
Treatment of a portion of the iodide dissolved in warm water with 10% aqueous perchloric acid gives a white solid which after cooling to 10C is filtered off, mp 137C to 138C;
see compound 2, Table ~. This mate~ial is also obtained directly by treating an aqueous solution of the methyl sulfate (above) with 10% sodium perchlorate and filtering off the product.
Example 13 Preparation of 1~2-Dimeth~1-3,~-dipiperidinopyrazolium bromide . _ . .
4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium bromide (6.3 g, 0.015 mole~ is dissolved in methanol (150 ml) and sodium hydroxide (1.2 g, 0.3 mole) and treated with 10%
palladium on carbon. The mixture is hydrogenated at 25C and absOrbs hydrogen; (290 ml) uncorrected (86%) in 25 minutes.
The catalyst is filtered off, washed with ethanol and aqueous hydrogen bromide (10 ml) is added. The mixture is evaporated in vacuo to an oil, which is dissolved in chloroform and pre-cipitated with diethyl ether to give a white powder on fil-tration mp ~11C. to 21^C, 3.4 g, (59 ). Anal,ysis see compound lO, Table IV.
A small amount of the bromide is dissolved in water and converted with 10% perchloric acid in quantitative yield to the perchlorate mp 171C to 172C, compound 11, Table IV.
Example 14 Following the procedure of Method A or Method B
3O above, there are obtained the compounds identified in Table IV in good yields and purity.
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1,2-Dimethyl-3-(2-methylpiperidino)- 500 2-Trace 5-phenylpyrazolium iodide 3-(Hexahydro-lH-azepin-l-yl)-1,2-500 3-Slight dimethyl-5-phenylpyrazolium iodide 1,2-Dimethyl-3-phenyl-5-piperidino- 500 3-Slight pyrazolium iodide From these data it is apparent that 1,2-dimethyl-3-(2,3 or 4-methylpiperidino)-5-phenylpyrazolium salts are preferred fungicidal agents effective for the control of powdery mildew on wheat.
The following examples illustrate the preparation of the compounds employed as fungicides herein.
~ 1 ..
~059~24 Example 3 Preparation of l-methyl-~-phenyl-2-pyrazolin-5-one Ethyl benzoylacetate (1,538 g, 8 moles) dissolved ln lsopropanol (5 1) is placed ln a 12 1 flask under an at-mosphere of nitrogen. Methylhydrazine (410 g, 8.7 moles, 98~) in isopropanol (800 ml) is added with stirring in a dropwise manner to the ethyl benzoylacetate solution pre-warmed to about 80C. During the addition the external heating is removed. Seeding of the reaction mixture with the product at the point of one-third addition of methyl-hydrazlne causes a copious precipitate of product. This procedure eliminates a large exotherm from occurring at a later stage. After the addition is complete~ the reaction mixture ls held at about 80C. for 2 hours. Cooling the slurry to 20C. and filtering off the solid, a yield of 1,131 g (81~) of product after drying with a melting point equal to 211C. is obtained.
Example 4 Preparation of 5-chloro-1-methyl-3-phenylpyrazole To a solution of phosphorous oxychloride (2,015 g, 19 moles) is added solid 1-methyl-3-phenyl?yrazolin-5-one (2,073 g, 11.9 moles) with stirring and warming. At 100C.
the mixture becomes homogeneous. The reflux temperature rises from 119C. to 143C. over a period of 30 hours. After coolln~ the mixture is poured into ice and water (8 1) with stirring. After 4 hours the slurry is filtered and the fllter cake added to 4 1 of water containing 1.5 1 of 10~ sodium hydroxide solution with stirring. Removal of the solid by filtration followed by a recrystallization from hexane yields 1,523 g of product, having a melting point ranging from 51C.
to 52C.
Example 5 Preparation of 3-chloro-1,2-dimethyl-5-~henylpyrazolium methyl sulfate, utilizing one of two methods METHOD (A) Dimethyl sulfate (30 g, 0.22 mole) is added to a stirred solution of 5-chloro-1-methyl-5-phenylpyrazole (39.5 g, 0.2 mole) in dry xylene (350 ml) and the reaction mixture is warmed to 105C. to 115C. for 18 hours. A brown syrup separates out, the reaction is cooled and the xylene is decanted off. Dry acetone (300 ml) is added and after stirring a white precipitate separates out and is filtered off, mp 100C. to 102C. 33.8 g, (55~). Recrystallization from dry acetone-toluene (1:1) gives white needles mp 102C.
to 104C.
Analysis calculated for C12H15N2ClSO4: C, 45.22;
H, 4.74; N, 8.79; Cl, 11.13. Found: C, 45.31; H, 4.81;
N, 8.93; Cl, 11.24.
METHOD (B) To a solution of dimethyl sulfate (1,596 g, 12.66 moles) at 70C. to 74C. is added 5-chloro-1-methyl-3-phenyl-pyrazole (1,523 g, 7.912 moles). During the exothermic ad-dition the heat source is removed. After the exothermic reaction has ceased, the reaction mixture is maintained at 80C. by external heating for 2 hours and then is poured into toluene. Toluene is decanted off, leaving a residual syrup, which is treated with additional toluene and decanted off as above. The syrup is dissolved in chloroform, filtered, and the filtrate evaporated to an oil, which crystallizes from acetone to yield 1.52 kg, (60.3%) mp 95C. to 96C.
Example 6 Preparation of 3-chloro 1,2-dimethyl-5-phenylpyrazolium iodide To an aqueous solution of 1,2-dimethyl-3-chloro-5-phenylpyrazolium methyl sulfate is added a saturated aqueous _ lOS90Z4 solution of sodium iodide at 5C. A copious precipitate is formed and filtered off. The solid is dissolved in methylene chloride and precipitated with diethyl ether to yield almost white crystals mp 152C. to 154C.
Analysis calculated for CllHl2N2Cll: C, 39.49;
H, 3.52; N, 8.38; Cl, 10.54; I, 37.93. Found: C, 39.45;
H, 3.51; N, 8.44; Cl, 10.47; I, 37.85.
Example 7 Preparation of ~-cyclohexyl-l-methyl-2-pyrazolin-5-one To ethyl 3-oxo-cyclohexanepropionic acid (4.4 g, 0.234 molej in n-propanol (500 ml) is added dropwise with stirring under nitrogen at 80C. methylhydrazine (13.8 g, 0.3 mole). After heating at reflux during 5 hours, the reaction is cooled and evaporated to a residual oil. Crystal-lization from ethylacetate ~ives a white powder mp 170.5C.
to 172C.
Analysis calculated for CloHloN20; C, 56.5~ H, 8.95; N, 15.54. Found: C, 55.59; H, 9.07; N, 15.~9.
Example 8 Preparation of 5-chloro-3-cyclohexyl~l-methylpyrazole Phosphoru~ oxychloride (15.3 g, 0.1 mole) is added to 3-cyclohexyl-1-methyl-2-pyrazolin-5-one and the mixture stirred and heated at 120C. to 135C. for 8 hours. The cooled reaction mixture is then poured into ice-water, made alkaline with 1~ aqueous sodium hydroxide and extracted with methylene chloride. Removal of solvent under reduced pressu~, then in vacuo at 70C. affords an oil, 8 g, (93.8~).
Analysis calculated for CloH15N~Cl; C, 50.45;
H, 7.51; N, 14.10; Cl, 17.85. Found: C, 50.c8; H, 7.55;
N, 14.20; Cl, 17.79.
_ ~4 -- : lOS9OZ4 Example 9 Preparation of 3-chloro-5-cyclohexyl-1,2-dimethylpyrazolium methyl sulfate ~and hydrogen sulfate (1:1)]
A mixture of 5-chloro-3-cyclohexyl-1-methylpyrazole (7 g, .0352 mole) and dimethyl sulfate (8.82 g, 0.07 mole) is heated to 80C. and the heating source then removed. The reaction temperature rises to ~8C. and then, after the exo-therm, the temperature is maintained at ~0C. by external heating for 5 hours. Toluene (100 ml) is added to the cooled reaction and the mixture is set aside overnight at room temperature and then a waxy solid is filtered off. Crystal-llzation from methylene chloride-ether affords a granular product, mp 70C. to 73.5C., 11.2 g (100%). NMR and infrared spectra indicate a mixture of CH3S04 and HS04 anions.
Analysis calculated for Cl2H2lN2ClS04 (as CH3S04):
C,44.35; H, 5.57-; N, 8.53; S, 9.&7; Cl, 10.92. Found C, 41.34;
H, 5.24; N, 8.14; S, 9.12; Cl, 10.31.
A portion of the above compound is readily converted to the perchlorate whose melting point ranges from 215C. to 218C.
Example 10 Preparation of 3,4,5-Tribromo-l-methylpyrazole _ .. . . . . .
To 3,4,5-tribromo?yrazole (4.5 g, 0.15 mole) in 3N
aqueous sodium hydroxide (5 g, 0.15 mole) is added at room temperature with stirring dimethyl sulfate (19 g, 0.15 mole).
After 10 minutes a solid separates out. An additional gram of dimethyl sulfate is added and the mixture is stirred for 3 days, filtered and the precipitate water washed and air dried to yield 33 g (73,0), mp 85C. to &5C. Crystallization from cyclohexane yields desired solid product whose melting point ranges from about 90C. to 91C.
Analysis calculated for C4H3N2Br3: C, 15.07; ~, o ~5;
N, 8.79; Br, 75. '1. Found: C, 15.1~; H, 0.~32; N, &.7; Br 75.35.
Example 11 ~rc b ~ r ~ t ~
A stirred suspension of l-methyl-3,4,5-tribromo-pyrazole (19.3 g, 0.05 mole) ln dimethyl sulfate (80 ml) is stirred and heated at 130C. to 135C. for 5 hours. On cooling and setting aside overnight, a solid is obtained and filtered off, benzene washed and ai~ dried to yield 18.7 g, (70~) whose melting point ranges from 199C. to 203C.
lo Analysis calculated for C~H~N2Br3SO4: C, 15.19;
H, 2.04; N, 5.?9; Br, 53.88; S, 7.20. Found: C, 16.19;
H, 1.99; N, 5.38; Br, 53.98; S, 7.31.
Treatment of the above methyl sulfate compound with aqueous perchloric acid affords the perchlorate whose melting point ranges from 300C. to 300.5C.
Example 12 Preparation of 1,2-dimethyl-3-phenyl-5-piperidinopyrazolium iodid~and perchlorate Piperidine (2.56 g, 0.03 mole) is added to 1,2-dimeth~
3-chloro-5-phenylpyrazolium methyl sulfate (4.77 g, 0.015 mole) in absolute ethanol (30 ml) and the mixture stirred with a bar magnet and heated under reflux for 4 hours. After cooling, the reaction mixture is evaporated under reduced pressure to a brown oil, and then dissolved in 50 ml of aqueous saturated sodium bicarbonate solution. The aqueous layer is extracted with ether and this organic layer discarded, then with chloro-form (3x100 ml). Evaporation of the chloroform layer affords 1,2-dimethyl-3-phenyl-5-piperidinopyrazolium methyl sulfate as a viscous oil. The oil is redissolved in water and saturated 3 aqueous potassium iodide solution is added. (Sodium iodide is also equally effective). An immediate copious white precipitat~
of 1,2-dimethyl-3-phenyl-5-piperidinopyrazolium iodide is formed, then filtered and washed with ice cold water to ~ive _ ~f _ ~ 1059024 3.37 g, (56%) Or product mp 179C to 180C. The melting point is unchanged by dissolving in chloroform, filterln~ and repre-cipitating with diethyl ether and filtering Orr the solid.
For analysis see Table ~, compound 1.
Treatment of a portion of the iodide dissolved in warm water with 10% aqueous perchloric acid gives a white solid which after cooling to 10C is filtered off, mp 137C to 138C;
see compound 2, Table ~. This mate~ial is also obtained directly by treating an aqueous solution of the methyl sulfate (above) with 10% sodium perchlorate and filtering off the product.
Example 13 Preparation of 1~2-Dimeth~1-3,~-dipiperidinopyrazolium bromide . _ . .
4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium bromide (6.3 g, 0.015 mole~ is dissolved in methanol (150 ml) and sodium hydroxide (1.2 g, 0.3 mole) and treated with 10%
palladium on carbon. The mixture is hydrogenated at 25C and absOrbs hydrogen; (290 ml) uncorrected (86%) in 25 minutes.
The catalyst is filtered off, washed with ethanol and aqueous hydrogen bromide (10 ml) is added. The mixture is evaporated in vacuo to an oil, which is dissolved in chloroform and pre-cipitated with diethyl ether to give a white powder on fil-tration mp ~11C. to 21^C, 3.4 g, (59 ). Anal,ysis see compound lO, Table IV.
A small amount of the bromide is dissolved in water and converted with 10% perchloric acid in quantitative yield to the perchlorate mp 171C to 172C, compound 11, Table IV.
Example 14 Following the procedure of Method A or Method B
3O above, there are obtained the compounds identified in Table IV in good yields and purity.
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Claims (13)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS;
1. A method for protecting plants from attack by fungi comprising: applying to said plants a fungicidally effective amount of a compound having a formula selected from the group consisting of:
(I) and (II) wherein R3 represents a member selected from the group consisting of hydrogen, methyl, hydroxy and phenyl; R4 represents a member selected from the group consisting of hydrogen, and halogen; R5 represents a member selected from the group consisting of phenyl, cyclohexyl and ; X represents an anion with a charge of 1 or 2; n represents an integer selected from 4, 5 and 6; m represents an integer selected from 1 and 2; and HB is an acid.
(I) and (II) wherein R3 represents a member selected from the group consisting of hydrogen, methyl, hydroxy and phenyl; R4 represents a member selected from the group consisting of hydrogen, and halogen; R5 represents a member selected from the group consisting of phenyl, cyclohexyl and ; X represents an anion with a charge of 1 or 2; n represents an integer selected from 4, 5 and 6; m represents an integer selected from 1 and 2; and HB is an acid.
2. The method according to Claim 1 wherein said compound is a formula (I) pyrazolium salt and the plants to be protected are cereal grain plants.
3. The method according to Claim 1 or 2 wherein the fungus organism is powdery mildew and the compound is applied in liquid form as a spray containing 100 ppm to 5600 ppm of the formula (I) pyrazolium salt compound.
4. The method according to Claim 1 or 2 wherein said compound is: 1,2-dimethyl-3-phenyl-5-piperidinopyrazolium iodide.
5. The method according to Claim 1 or 2 wherein the compound is: 1,2-dimethyl-3-phenyl-5-piperidinopyrazolium perchlorate.
6. The method according to Claim 1 or 2 wherein the compound is: 1,2-dimethyl-3-phenyl-5-(1-pyrrolidinyl)pyrazolium methyl sulfate.
7. The method according to Claim 1 or 2 wherein the compound is: 3-(hexahydro-1H-azepin-1-yl)-1,2-dimethyl-5-phenylpyrazolium iodide.
8. The method according to Claim 1 or 2 wherein the compound is: 1,2-dimethyl-3-(4-methylpiperidino)-5-phenylpyrazolium iodide.
9. The method according to Claim 1 or 2 wherein the compound is: 4-bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium bromide.
10. The method according to Claim 1 or 2 wherein the compound is: 1,2-dimethyl-3,5-dipiperidinopyrazolium perchlorate.
11. The method according to Claim 1 or 2 wherein the compound is: 1,2-dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium perchlorate.
12. A method for controlling fungi by contacting said fungi with a fungicidally effect amount of a compound according to Claim 1 having a formula selected from the group consisting of:
(I) and (II) wherein R3 represents a member selected from the group con-sisting of hydrogen, methyl, hydroxy and phenyl; R4 repre-sents a member selected from the group consisting of hydrogen, and halogen; R5 represents a member selected from the group consisting of phenyl, cyclohexyl and ; X represents an anion with a charge of 1 or 2; n represents an integer selected from 4, 5 and 6; m represents an integer selected from 1 and 2; and HB is an acid.
(I) and (II) wherein R3 represents a member selected from the group con-sisting of hydrogen, methyl, hydroxy and phenyl; R4 repre-sents a member selected from the group consisting of hydrogen, and halogen; R5 represents a member selected from the group consisting of phenyl, cyclohexyl and ; X represents an anion with a charge of 1 or 2; n represents an integer selected from 4, 5 and 6; m represents an integer selected from 1 and 2; and HB is an acid.
13. A method according to Claim 12 wherein the fungus organism is powdery mildew and the compound is applied in liquid form as a spray containing 100 ppm to 5600 ppm of the formula (I) pyrazolium salt compound.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/556,748 US3970754A (en) | 1975-03-10 | 1975-03-10 | 1,2-Dialkyl-3(or 3,5)-N-heterocyclic pyrazolium salts of derivatives thereof as fungicidal agents |
| US05/574,795 US4029492A (en) | 1975-03-10 | 1975-05-05 | Novel 1,2-dialkylpyrazolium compounds having 3-(or 3,5-) nitrogen-containing heterocyclic group as herbicides |
| US05/683,562 US4044013A (en) | 1975-03-10 | 1976-05-05 | 1,2-Dialkylpyrazolium compounds having 3-(or 3,5-) nitrogen-containing heterocyclic group |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1059024A true CA1059024A (en) | 1979-07-24 |
Family
ID=27415731
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA247,245A Expired CA1070303A (en) | 1975-03-10 | 1976-03-05 | 1,2-dialkylpyrazolium compounds having 3-(or 3,5-) nitrogen-containing heterocyclic group as herbicides |
| CA247,510A Expired CA1059024A (en) | 1975-03-10 | 1976-03-09 | 1,2-dialkyl-3(or 3,5)-n-heterocyclic pyrazolium salts or derivatives thereof as fungicidal agents |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA247,245A Expired CA1070303A (en) | 1975-03-10 | 1976-03-05 | 1,2-dialkylpyrazolium compounds having 3-(or 3,5-) nitrogen-containing heterocyclic group as herbicides |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US3970754A (en) |
| JP (1) | JPS51125385A (en) |
| BE (1) | BE839377A (en) |
| CA (2) | CA1070303A (en) |
| CH (1) | CH625237A5 (en) |
| DE (1) | DE2609961A1 (en) |
| FR (1) | FR2303804A1 (en) |
| GB (1) | GB1536493A (en) |
| NL (1) | NL7602520A (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4091106A (en) * | 1976-06-09 | 1978-05-23 | American Cyanamid Company | 1,2-Dialkyl-3(or 3,5)-N-heterocyclic pyrazolium salts or derivatives thereof as fungicidal agents |
| US4957536A (en) * | 1980-06-02 | 1990-09-18 | American Cyanamid Company | Method for increasing axillary branching, tillering, flowering and yield of agronomic and horticultural crops with certain 2-(2-imidazolin-2-yl)-pyridines and quinolines |
| US4404012A (en) * | 1980-06-02 | 1983-09-13 | American Cyanamid Company | Process for increasing sugar yield in sugarcane |
| US4450278A (en) * | 1982-06-28 | 1984-05-22 | Chevron Research Company | Intermediates for 1-methyl-3,4-dihalo-5-thio-(2-hydroxyethyl)-pyrazole |
| EP0209230B1 (en) | 1985-05-30 | 1991-02-27 | E.I. Du Pont De Nemours And Company | Herbicidal sulfonamides |
| US4911753A (en) * | 1987-01-21 | 1990-03-27 | American Cyanamid Company | Herbicidal 2-(2-imidazolin-2-yl)fluoroalkoxy-, alkenyloxy-, and alkynyloxypyridines and quinolines |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3752816A (en) * | 1969-06-10 | 1973-08-14 | Sherwin Williams Co | Certain 3-substituted-pyrido(3,2-d)pyrimidine 2,4-(1h,3h)-diones |
| US3780046A (en) * | 1970-02-24 | 1973-12-18 | Exxon Research Engineering Co | Herbicidal n-(2-picolyl) substituted 2,6-dinitroanilines |
| US3766172A (en) * | 1971-07-01 | 1973-10-16 | Monsanto Co | Substituted dichlorosulfenamides and their manufacture |
| DE2260485C2 (en) * | 1971-12-17 | 1983-12-29 | American Cyanamid Co., Wayne, N.J. | 1,2-dialkyl-3,5-diphenylpyrazolium salts and herbicidal agents containing them |
| US3882142A (en) * | 1972-07-13 | 1975-05-06 | American Cyanamid Co | 1,2-Dialkyl-3,5-diphenyl pyrazolium salts |
| US3963742A (en) * | 1974-07-12 | 1976-06-15 | American Cyanamid Company | 1,2-Dialkyl-3,4,5-trisubstituted pyrazolium salts as herbicidal agents |
| US3941881A (en) * | 1975-03-14 | 1976-03-02 | American Cyanamid Company | Novel 3 or 5-aminopyrazolium salts and fungicidal use thereof |
| US3963741A (en) * | 1975-05-02 | 1976-06-15 | American Cyanamid Company | 4-Alkyl-1,2-dimethyl-3,5-diphenylpyrazolium salts and derivatives thereof as fungicidal agents |
-
1975
- 1975-03-10 US US05/556,748 patent/US3970754A/en not_active Expired - Lifetime
- 1975-05-05 US US05/574,795 patent/US4029492A/en not_active Expired - Lifetime
-
1976
- 1976-03-03 GB GB8530/76A patent/GB1536493A/en not_active Expired
- 1976-03-05 CA CA247,245A patent/CA1070303A/en not_active Expired
- 1976-03-09 CA CA247,510A patent/CA1059024A/en not_active Expired
- 1976-03-09 FR FR7606729A patent/FR2303804A1/en active Granted
- 1976-03-09 CH CH291076A patent/CH625237A5/de not_active IP Right Cessation
- 1976-03-10 DE DE19762609961 patent/DE2609961A1/en not_active Withdrawn
- 1976-03-10 BE BE164999A patent/BE839377A/en not_active IP Right Cessation
- 1976-03-10 NL NL7602520A patent/NL7602520A/en not_active Application Discontinuation
- 1976-03-10 JP JP51025987A patent/JPS51125385A/en active Pending
- 1976-05-05 US US05/683,562 patent/US4044013A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| FR2303804A1 (en) | 1976-10-08 |
| JPS51125385A (en) | 1976-11-01 |
| US4044013A (en) | 1977-08-23 |
| FR2303804B1 (en) | 1982-11-26 |
| NL7602520A (en) | 1976-09-14 |
| CA1070303A (en) | 1980-01-22 |
| US3970754A (en) | 1976-07-20 |
| GB1536493A (en) | 1978-12-20 |
| CH625237A5 (en) | 1981-09-15 |
| BE839377A (en) | 1976-09-10 |
| DE2609961A1 (en) | 1976-09-30 |
| US4029492A (en) | 1977-06-14 |
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